Data Sheet
Cefazolin-AFT
Cefazolin sodium Ph Eur powder for injection equivalent to Cefazolin
500 mg, 1 g and 2g
Presentation
Cefazolin-AFT 500 mg, 1 g and 2 g vials contain a white to off-white powder
which reconstitutes with Sterile Water for Injection to give a colourless solution.
Cefazolin-AFT 500 mg vial contains cefazolin sodium equivalent to 500 mg of
cefazolin.
Cefazolin-AFT 1 g vial contains cefazolin sodium equivalent to 1 g of cefazolin.
Cefazolin-AFT 2 g vial contains cefazolin sodium equivalent to 2 g of cefazolin.
Uses
Actions
Cefazolin sodium is a semisynthetic cephalosporin for intramuscular or intravenous
administration. In vitro tests demonstrate that the bactericidal action of
cephalosporins results from inhibition of cell-wall synthesis.
Cefazolin is active against the following organisms in vitro and in clinical infections:
Staphylococcus aureus (including penicillinase-producing strains)
Staphylococcus epidermidis.
Group -haemolytic streptococci and other strains of streptococci (many strains of
enterococci are resistant).
Streptococcus pneumoniae
Escherichia coli
Klebsiella sp.
Proteus mirabilis
Haemophilus influenzae
Enterobacter aerogenes
Most strains of indole-positive Proteus (Proteus vulgaris), Enterobacter cloacae,
Morganella morganii, and Providencia rettgeri are resistant.
Methicillin-resistant staphylococci, Serratia, Pseudomonas and Acinetobacter
calcoaceticus (formerly Mima and Herellea sp.) are almost uniformly resistant to
cefazolin.
Disc Susceptibility Tests:
Quantitative methods that require measurements of zone diameters give the most
precise estimates of antibiotic susceptibility. One such procedure has been
recommended for use with discs for testing susceptibility to cefazolin. With this
procedure, a report from the laboratory of “susceptible” indicates that the infecting
organism is likely to respond to therapy. A report of “resistant” indicates that the
infecting organism is not likely to respond to therapy. A report of “moderately
susceptible” suggests that the organism would be susceptible if high dosage is used
or if the infection were confined to tissues and fluids (e.g. urine) in which high
antibiotic levels are attained.
For gram-positive isolates, a zone of 18 mm is indicative of a cefazolin-susceptible
organism when tested with either the cephalosporin-class disc (30 mcg cephalothin)
or the cefazolin disc (30 mcg cefazolin).
Gram-negative organisms should be tested with the cefazolin disc (using the above
criteria) because cefazolin has been shown by in vitro tests to have activity against
certain strains of Enterobacteriaceae found to be resistant when tested with the
cephalothin disc. When using the cephalothin disc, Gram-negative organisms with
zone diameters >18 mm may be considered susceptible to cefazolin however
organisms with zone diameters < 18 mm are not necessarily resistant or moderately
susceptible to cefazolin.
The cefazolin disc should not be used for testing susceptibility to other
cephalosporins.
Dilution Techniques:
A bacterial isolate should be considered susceptible if the minimal inhibitory
concentration (MIC) for cefazolin is < 16 mcg/mL. Organisms are considered
resistant if the MIC is > 64 mcg/mL.
Pharmacokinetics
Table 1 demonstrates the blood levels and duration of cefazolin following
intramuscular administration.
Table 1 – Serum concentrations after intramuscular administration.
Dose
Serum Concentrations (mcg/mL)
½ Hr
1 Hr
2 Hr
4 Hr
6 Hr
250 mg
15.5
17
13
5.1
2.5
500 mg
36.2
36.8
37.9
15.5
6.3
1 g*
60.1
63.8
54.3
29.3
13.2
* Average of 2 studies
8 Hr
3
7.1
Clinical pharmacology studies in patients hospitalised with infections indicate that
cefazolin produces mean peak serum levels approximately equivalent to those seen
in normal volunteers.
In a study (using normal volunteers) of constant intravenous infusion with dosages of
3.5 mg/kg for 1 hour (approximately 250 mg) and 1.5 mg/kg for the next 2 hours
(approximately 100 mg), cephazolin produced a steady serum level at the third hour
of approximately 28 mcg/mL.
Table 2 shows the average serum concentrations after IV injection of a single 1g
dose: average half-life was 1.4 hours.
Table 2 – Serum concentrations after 1g intravenous dose.
Serum Concentration (mcg/mL)
5 min
15 min
30 min
1 Hr
2 Hr
188.4
135.8
106.8
73.7
45.6
4 Hr
16.5
Controlled studies in adult normal volunteers receiving 1 g, 4 times a day, for 10
days, monitoring CBC, AST, ALT, bilirubin, alkaline phosphatase, BUN, creatinine,
and urinalysis indicated no clinically significant changes attributed to cefazolin.
Cefazolin is excreted unchanged in the urine primarily by glomerular filtration and, to
a lesser degree, by tubular secretion. Following intramuscular injection of 500mg,
56% to 89% of the administered dose is recovered within 6 hours, and 80% to nearly
100% in 24 hours. Cefazolin achieves peak urine concentrations greater than 1000
mcg/mL and 4000 mcg/mL, respectively, following 500 mg and 1 g intramuscular
doses.
In patients undergoing peritoneal dialysis (2 L/hr) mean serum levels of cefazolin
were approximately 10 and 30 mcg/mL after 24 hours’ instillation of a dialysing
solution containing 50 mcg/mL and 150 mcg/mL, respectively. Mean peak levels
were 29 mcg/mL (range 13-44 mcg/mL) with 50 mcg/mL (3 patients), and 72 mcg/mL
(range 26-142 mcg/mL) with 150 mcg/mL (6 patients). Intraperitoneal administration
of cefazolin is usually well tolerated.
When cefazolin is administered to patients with unobstructed biliary tracts, high
concentrations well above serum levels occur in the gall-bladder tissue and bile. In
the presence of obstruction, however, concentration of the antibiotic is considerably
lower in bile than the serum.
Cefazolin readily crosses an inflamed synovial membrane, and the concentration of
the antibiotic achieved in the joint space is comparable to levels measured in the
serum.
Cefazolin readily crosses the placental barrier into the cord blood and amniotic fluid.
It is present in very low concentrations in the milk of nursing mothers.
Indications
Cefazolin-AFT is indicated in the treatment of the following serious infections due to
susceptible organisms:
Respiratory Tract Infection:
Due to S. pneumoniae, Klebsiella sp, H. influenzae, Staph, aureus (including
penicillinase-producing strains), and Group -haemolytic streptococci.
Injectable penicillin G benzathine is considered to be the medicine of choice in the
treatment and prevention of streptococcal infections, including the prophylaxis of
rheumatic fever.
Cefazolin-AFT is effective in the eradication of streptococci from the nasopharynx;
however, data establishing the efficacy of cephazolin in the subsequent prevention of
rheumatic fever are not available at present.
Genitourinary Tract Infections:
Due to E. coli, P. mirabilis, Klebsiella sp., and some strains of Enterobacter and
enterococci.
Skin and Soft-tissue Infections:
Due to Staph. aureus (including penicillinase-producing strains) and Group A βhaemolytic streptococci and other strains of streptococci.
Biliary Tract Infections:
Due to E. coli, various strains of streptococci, P. mirabilis, Klebsiella sp., and Staph.
aureus.
Bone and Joint Infections:
Due to Staph. aureus.
Septicaemia:
Due to S. pneumoniae, Staph. aureus (penicillin-susceptible and penicillin-resistant).
P. mirabilis, E. coli, and Klebsiella sp.
Endocarditis:
Due to Staph. aureus (penicillin-susceptible and penicillin-resistant) and Group A haemolytic streptococci.
Appropriate culture and susceptibility studies should be performed to determine
susceptibility of the causative organism to Cefazolin-AFT.
Perioperative Prophylaxis:
The prophylactic administration of Cefazolin-AFT preoperatively, intraoperatively, and
postoperatively may reduce the incidence of certain post-operative infections in
patients undergoing surgical procedures that are classified as contaminated or
potentially contaminated (e.g vaginal hysterectomy, or cholecystectomy in high-risk
patients, such as those over 70 years of age who have acute cholecystitis,
obstructive jaundice, or common bile-duct stones).
The perioperative use of Cefazolin-AFT may also be effective in surgical patients in
whom infection at the operative site would present a serious risk (e.g. during openheart surgery and prosthetic arthroplasty).
The prophylactic administration of Cefazolin-AFT should usually be discontinued
within a 24 hour period after the surgical procedure. For surgery in which the
occurrence of infection may be particularly devastating (e.g. open-heart surgery and
prosthetic arthroplasty), the prophylactic administration of Cefazolin-AFT may be
continued for 3 to 5 days following the completion of surgery. If there are signs of
infection, specimens for cultures should be obtained for the identification of the
causative organism so that appropriate therapy may be instituted.
Dosage and Administration
Cefazolin-AFT may be administered intramuscularly or intravenously after
reconstitution. Total daily dosages are the same for either route of administration.
The intrathecal administration of Cefazolin-AFT is not an approved route of
administration for this antibiotic. There have been reports of severe CNS toxicity
including seizes when cefazolin has been administered in this manner.
Intramuscular Administration:
Reconstitute as directed in Table 3. Shake well until dissolved. The 500 mg vial can
be reconstituted with 0.9% Sodium Chloride Injection, Sterile Water for Injection or
Bacteriostatic Water for Injection. The 1 g a n d 2 g vial should only be
reconstituted with Sterile Water for Injection or Bacteriostatic Water for Injection.
Cefazolin-AFT should be injected into a large muscle mass. Pain on injection is
infrequent with Cefazolin-AFT.
Table 3 – Dilution Table
Vial Size
Diluent to be
Added
500mg
2 mL
1g*
2.5 mL
2g
20 mL
Approx. Available
Volume
2.2 mL
3 mL
1.8mL
Approx. Average
Concentration
225 mg/mL
330 mg/mL
96 mg/mL
Intravenous Administration:
Cefazolin-AFT may be administered by intravenous injection or by continuous or
intermittent infusion.
Intermittent Intravenous Infusion:
Cefazolin-AFT may be administered along with primary intravenous fluid
management programmes in a volume control set or in a separate, secondary IV
bottle. Reconstituted 500 mg, 1 g or 2g of Cefazolin-AFT may be diluted in 50 to 100
mL of one of the following intravenous solutions: 0.9% Sodium Chloride Injection, 5%
or 10% Dextrose Injection, 5% Dextrose in Lactated Ringer’s Injection, 5%
Dextrose and 0.9% Sodium Chloride Injection (also may be used with 5% Dextrose
and 0.45% or 0.2% Sodium Chloride Injection), Lactated Ringer’s Injection, 5% or
10% Invert Sugar in Sterile Water for Injection, Ringer’s Injection, Normosol-M in
D5-W, Ionosol B with Dextrose 5% or Plasma-Lyte with 5% Dextrose.
Intravenous Injection:
Administer solution directly into vein or through tubing. Dilute the reconstituted 500
mg, 1 g or 2g of Cefazolin-AFT in a minimum of 10 mL of Sterile Water for
Injection. Inject solution slowly over a period of 3 to 5 minutes. Do not inject in
less than 3 minutes.
Dosage:
The usual adult dosages are given in Table 4. In rare instances, doses up to 12g of
cefazolin per day been used.
Table 4 – Usual Adult Dosage
Type of Infection
Pneumococcal pneumonia
Mild infections caused by susceptible grampositive cocci
Acute uncomplicated urinary tract infections
Moderate to severe infections
Severe,
life
threatening
infections
(e.g.
endocarditis and septicaemia)*
Dose
500 mg
250-500 mg
Frequency
12 hourly
8 hourly
1g
500 mg-1 g
1 g-1.5 g
12 hourly
6-8 hourly
6 hourly
Dosage adjustment for Patients with Reduced Renal Function:
Cefazolin-AFT may be used in patients with reduced renal function with the following
dosage adjustments: Patients with a creatinine clearance > 55 mL/min or a serum
creatinine < 1.5 mg% can be given full doses. Patients with creatinine clearance
rates of 35 to 54 mL/min or serum creatinine of 1.6 to 3.0 mg % can also be given full
doses but dosage should be restricted to at least 8-hour intervals. Patients with
creatinine clearance rates of 11 to 34 mL/min or serum creatinine of 3.1 to 4.5 mg %
should be given half the usual dose every 12 hours. Patients with creatinine
clearance rates < 10mL/min or serum creatinine > 4.6mg % should be given half the
usual dose every 18 to 24 hours. All reduced dosage recommendations apply after
an initial loading dose appropriate to the severity of the infection. For information
about peritoneal dialysis, see Pharmacokinetics.
Perioperative Prophylactic Use:
To prevent postoperative infection in contaminated or potentially contaminated
surgery, the recommended doses are as follows:
 1 g IV or IM administered 30 minutes to 1 hour prior to the start of surgery;
 For lengthy operative procedures (e.g. 2 hours or longer), 0.5 to 1 g IV or IM
during surgery (administration modified according to the duration of the operative
procedure);
 0.5 to 1g IV or IM every 6 to 8 hours for 24 hours postoperatively.
It is important that:
 The preoperative dose be given 30 minutes to 1 hour prior to the start of surgery
so that adequate antibiotic levels are present in the serum and tissues at the time
of the initial surgical incision and
 If exposure to infections organisms is likely, Cefazolin-AFT be administered at
appropriate intervals during surgery in order that sufficient levels of the antibiotic
be present when needed.
In surgery in which infection may be particularly devastating (e.g. open heart surgery
and prosthetic arthroplasty), the prophylactic administration of Cefazolin-AFT may be
continued for 3 to 5 days following the completion of surgery.
Children:
In children, a total daily dosage of 25 to 50 mg/kg of body weight, divided into 3 or 4
equal doses, is effective for most mild to moderately severe infections (Table 5).
Total daily dosage may be increased to 100 mg/kg of body weight for severe
infections.
Table 5 – Paediatric dosage guide
Weight
25 mg/kg day
Divided into 3 doses
kg
Approx. single
Vol (mL)
needed with
dose
(mg 8 hourly)
dilution of
125mg/mL
4.5
40 mg
0.35 mL
9
75 mg
0.6 mL
13.6
115 mg
0.9 mL
18.1
150 mg
1.2 mL
22.7
190 mg
1.5 mL
Weight
50 mg/kg day
Divided into 3 doses
kg
Vol (mL)
Approx. single
needed with
dose
dilution of
(mg 8 hourly)
225mg/mL
4.5
75 mg
0.35 mL
9
150 mg
0.7 mL
13.6
225 mg
1 mL
18.1
300 mg
1.35 mL
22.7
375 mg
1.7 mL
25 mg/kg/day
Divided into 4 doses
Approx. single
Vol (mL)
needed with
dose
(mg 6 hourly)
dilution of
125mg/mL
30 mg
0.25 mL
55 mg
0.45 mL
85 mg
0.7 mL
115 mg
0.9 mL
140 mg
1.1 mL
25 mg/kg/day
Divided into 4 doses
Vol (mL)
Approx. single
needed with
dose
dilution of
(mg 6 hourly)
225mg/mL
55 mg
0.25 mL
110 mg
0.5 mL
170 mg
0.75 mL
225 mg
1 mL
285 mg
1.25 mL
In children with mild to moderate renal impairment (creatinine clearance of 70 to 40
mL/min), 60% of the normal daily dose given in divided doses every 12 hours should
be sufficient. In children with moderate impairment (creatinine clearance of 40 to 20
mL/min), 25% of the normal daily dose given in divided doses every 12 hours should
be sufficient. In children with severe impairment (creatinine clearance of 20 to 5
mL/min), 10% of the normal daily dose given every 24 hours should be adequate. All
dosage recommendations apply after an initial loading dose is administered.
Since safety for use in premature infants and in infants under 1 month of age has not
been established, the use of Cefazolin-AFT in these patients is not recommended.
Intraperitoneal administration:
Intraperitoneal administration of cefazolin is usually well tolerated.
Contraindications
Patients with known allergy to the cephalosporin group of antibiotics.
Warnings and Precautions
Warnings
Before Cefazolin-AFT therapy is instituted, careful inquiry should be made
concerning previous hypersensitivity reactions to cephalosporins and penicillin.
Cephalosporin C derivatives should be given cautiously to penicillin-sensitive
patients. Serious acute hypersensitivity reactions may require adrenaline and other
emergency measures.
There is some clinical and laboratory evidence of partial cross-allergenicity between
the penicillins and the cephalosporins. Patients have been reported to have had
severe reactions (including anaphylaxis) to both medicines.
Antibiotics, including Cefazolin-AFT should be administered cautiously to any patient
who has demonstrated some form of allergy, particularly to medicines.
Pseudomembranous colitis has been reported with virtually all broad-spectrum
antibiotics (including macrolides, semisynthetic penicillins, and cephalosporins). It is
important to consider its diagnosis in patients who develop diarrhoea in association
with the use of antibiotics. Such colitis may range in severity from mild to life
threatening. In moderate to severe cases, appropriate measures should be taken.
Usage in Infants:
Safety for use in premature infants and infants under one month of age has not been
established.
Precautions
General:
If an allergic reaction to Cefazolin-AFT occurs, the medicine should be discontinued
and the patient treated with the usual agents e.g. adrenaline or other pressor amines,
antihistamines, or corticosteroids.
Prolonged use of Cefazolin-AFT may result in the overgrowth of nonsusceptible
organisms. Careful clinical observation of the patient is essential. If superinfection
occurs during therapy, appropriate measures should be taken.
When Cefazolin-AFT is administered to patients with low urinary output because of
impaired renal function, lower daily dosage is required.
The intrathecal administration of Cefazolin-AFT is not an approved route of
administration for this antibiotic., There have been reports of severe central nervous
system (CNS) toxicity including seizures when cefazolin was administered in this
manner.
Broad spectrum antibiotics should be prescribed with caution in individuals with a
history of gastrointestinal disease, particularly colitis.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Mutagenicity studies and long-term studies in animals to determine the carcinogenic
potential of Cefazolin-AFT have not been performed.
Use during Pregnancy and Lactation
Category B1
Reproduction studies have been performed in rats given doses of 500 mg or 1 g of
cefazolin/kg bodyweight and have revealed no evidence of impaired fertility or harm
to the foetus due to cefazolin. There are, however, no adequate and well-controlled
studies in pregnant women. Because animal reproduction studies are not always
predictive of human response, this medicine should be used during pregnancy only if
clearly needed.
When Cefazolin-AFT has been administered prior to caesarean section, medicine
levels in cord blood have been approximately one-fourth to one-third of maternal
medicine levels. The medicine appears to have no adverse effect on the foetus.
Cefazolin-AFT is present in very low concentrations in the milk of nursing mothers.
Caution should be exercised when Cefazolin-AFT is administered to a nursing
woman.
Effects on ability to drive and use machines
This medicine is presumed to be safe or unlikely to produce an effect.
Adverse Effects
The following reactions have been reported:
Hypersensitivity:
Medicine fever, skin rash, vulvar pruritus, eosinophilia, Stevens-Johnson syndrome
and anaphylaxis
Blood:
Neutropenia, leucopenia, thrombocytopenia, thrombocythaemia and positive direct
and indirect Coombs’ tests have occurred.
Renal:
Transient rise in BUN levels has been observed without clinical evidence of renal
impairment. Interstitial nephritis and other renal disorders have been reported rarely.
Most patients experiencing these effects have been seriously ill and were receiving
multiple medicine therapies. The role of Cefazolin-AFT in the development of
nephropathies has not been determined.
Hepatic:
Transient rise in AST, ALT, and alkaline phosphatase levels have been observed
rarely. As with some penicillins and some other cephalosporins transient hepatitis
and cholestatic jaundice have been reported rarely.
Gastrointestinal:
Symptoms of pseudomembranous colitis may appear either during or after antibiotic
treatment. Nausea and vomiting have been reported rarely. Anorexia, diarrhoea and
oral candidiasis (oral thrust) have been reported.
Other:
Pain on intramuscular injection, sometimes with induration, has occurred
infrequently. Phlebitis at the site of injection has been noted. Other reactions have
included genital and anal pruritus, genital moniliasis, and vaginitis.
Interactions
Used concurrently, probenecid may decrease renal tubular secretion of
cephalosporins resulting in increased and more prolonged cephalosporin blood
levels.
A false-positive reaction for glucose in the urine may occur with Benedict’s solution,
Fehling’s solution, or CLINITEST Tablets, but not with enzyme-based tests, such as
CLINISTIX and TES-TAPE.
Positive direct and indirect antiglobulin (Coombs’) tests have occurred; these may
also occur in neonates whose mothers received cephalosporins before delivery.
Cefazolin-AFT should not be mixed in the syringe with aminoglycoside antibiotics.
Overdosage
Symptoms
Toxic signs and symptoms following an overdose of Cephazolin may include pain,
inflammation, and phlebitis at the injection site. The administration of inappropriately
large doses of parenteral cephalosporins may cause dizziness, paresthesias, and
headaches. Seizures may occur following overdosage with some cephalosporins,
particularly in patients with renal impairment in whom accumulation is likely to occur.
Laboratory abnormalities that may occur after an overdose include elevations in
creatinine, BUN, liver enzymes and bilirubin, a positive Coombs’ test,
thrombocytosis, thrombocytopenia, eosinophilia, leukopenia, and prolongation of the
prothrombin time.
Treatment
In managing overdosage, consider the possibility of multiple medicine overdoses,
interaction between medicines, and unusual medicine kinetics in your patient.
If seizures occur, the medicine should be discontinued promptly; anticonvulsant
therapy may be administered if clinically indicated. Protect the patient’s airway and
support ventilation and perfusion. Meticulously monitor and maintain, within
acceptable limits, the patient’s vital signs, blood gases, serum electrolytes, etc.
In cases of severe overdosage, especially in a patient with renal failure, combined
haemodialysis and haemoperfusion may be considered if response to more
conservative therapy fails. However, no data supporting such therapy are available.
Pharmaceutical Precautions
Store below 25 °C.
Stability:
In those situations in which the medicine and the diluent have been mixed, but not
immediately administered to the patient, the admixture may be stored under the
following conditions:
Reconstituted Cefazolin-AFT diluted in Sterile Water for Injection, 5% Dextrose
Injection, 0.9% Sodium Chloride Injection, or Bacteriostatic Water for Injection is
stable for 12 hours at room temperature and for 24 hours if stored under refrigeration
(2-8 oC).
Solutions of Cefazolin-AFT in 10% Dextrose Injection, 5% Dextrose in Lactated
Ringer’s Injection, 5% Dextrose and 0.9% Sodium Chloride Injection (also may be
used with 5% Dextrose and 0.45% or 0.2% Sodium Chloride Injection), Lactated
Ringer’s Injection, 5% or 10% Invert Sugar in Sterile Water for Injection, Ringer’s
Injection, Normosol-M in D5-W, Ionosol-B with Dextrose 5%, or Plasma-Lyte with 5%
Dextrose should be used within 12 hours after dilution if stored at room temperature
or within 24 hours if stored under refrigeration (2-8 oC).
Do not freeze reconstituted Cefazolin-AFT.
To reduce microbiological hazards, use as soon as practicable after reconstitution.
Cefazolin-AFT does not contain any anti-microbial agents and is intended for single
use in one patient only. Discard any residue. Prior to administration, parenteral
medicine products should be inspected visually for particulate matter and
discolouration whenever solution and container permit.
Medicines Classification
Prescription medicine
Package Quantities
500mg, 1g and 2g:
Packs of 1, 5 and 10 vials
Further Information
The pH of the reconstituted solution is between 4.5 and 6. Each gram of cefazolin
sodium contains 48.3 mg of sodium.
Name and Address
AFT Pharmaceuticals Ltd
PO Box 33.203
Takapuna
Auckland
Email:[email protected]
Date of Preparation
29 January 2016